| Title | Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism |
|---|---|
| Author | Viridiana Alejandre‑Castañeda1†, J. Alberto Patiño‑Medina1†, Marco I. Valle‑Maldonado2, Alexis García3, Rafael Ortiz‑Alvarado1, León F. Ruíz‑Herrera1, Karla Viridiana Castro‑Cerritos4, Joel Ramírez‑Emiliano5, Martha I. Ramírez‑Díaz1, Victoriano Garre6, Soo Chan Lee3, and Víctor Meza‑Carmen1* |
| Address | 1Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, 58030 Morelia, Mexico, 2Laboratorio Estatal de Salud Pública del Estado de Michoacán, 58279 Morelia, Mexico, 3Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases (STCEID), The University of Texas at San Antonio, San Antonio 78249, USA, 4Instituto de Química Aplicada, Universidad Papaloapan, Campus Tuxtepec, 68301 Tuxtepec, Mexico, 5Departamento de Ciencias Médicas, Universidad de Guanajuato, 37320 León, Mexico, 6Departamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain |
| Bibliography | Journal of Microbiology, 61(12),1043–1062, 2023, |
| DOI | /10.1007/s12275-023-00096-8 |
| Key Words | Dimorphism · Fungal virulence · Mucorales · Tec proteins · PKA pathway |
| Abstract | Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus. |